Laura E Targownik1,2, Eric I Benchimol3,4,5, Charles N Bernstein1, Harminder Singh1,6, Aruni Tennakoon1, Antonio Aviña Zubieta7, Stephanie Coward8, Jennifer Jones9, Gilaad G Kaplan8, M Ellen Kuenzig5, Sanjay K Murthy10, Geoffrey C Nguyen2,11, Juan Nicolás Peña-Sánchez12. 1. Section of Gastroenterology, Division of Internal Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 2. Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Ontario, Canada. 3. Children's Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada. 4. Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada. 5. ICES, Toronto, Canada. 6. Department of Community Health Sciences, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 7. Arthritis Research Centre, University of British Columbia, Vancouver British Columbia, Canada. 8. Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. 9. Department of Internal Medicine, Dalhousie University, Halifax, NS, Canada. 10. The Ottawa Hospital IBD Centre, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada. 11. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. 12. Department of Community Health & Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Abstract
BACKGROUND AND AIMS: The combination of infliximab and azathioprine is more efficacious than either therapy alone for Crohn's disease [CD] and ulcerative colitis [UC]. However, it is uncertain whether these benefits extend to real-world clinical practice and to other combinations of biologics and immunomodulators. METHODS: We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect. RESULTS: In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66-0.90; UC: aHR 0.72, 95% CI 0.62-0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02-2.28]) but not CD (aHR = 1.22 [95% CI 0.96-1.54]). CONCLUSION: In an analysis of a database of real-world patients with IBD, combination therapy decreased the likelihood of treatment failure in both CD and UC.
BACKGROUND AND AIMS: The combination of infliximab and azathioprine is more efficacious than either therapy alone for Crohn's disease [CD] and ulcerative colitis [UC]. However, it is uncertain whether these benefits extend to real-world clinical practice and to other combinations of biologics and immunomodulators. METHODS: We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect. RESULTS: In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66-0.90; UC: aHR 0.72, 95% CI 0.62-0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02-2.28]) but not CD (aHR = 1.22 [95% CI 0.96-1.54]). CONCLUSION: In an analysis of a database of real-world patients with IBD, combination therapy decreased the likelihood of treatment failure in both CD and UC.
Authors: Johannes P D Schultheiss; Remi Mahmoud; Jonas M Louwers; Michiel T van der Kaaij; Boris P van Hellemondt; Petra G van Boeckel; Nofel Mahmmod; Bindia Jharap; Herma H Fidder; Bas Oldenburg Journal: Aliment Pharmacol Ther Date: 2021-09-24 Impact factor: 9.524
Authors: Siddharth Singh; Deborah Proctor; Frank I Scott; Yngve Falck-Ytter; Joseph D Feuerstein Journal: Gastroenterology Date: 2021-06 Impact factor: 33.883